Factors associated with mortality in severely malnourished hospitalized children who developed septic shock.

INTRODUCTION: Septic shock can often lead to death, even in resourceful settings, if not handled carefully. Therefore, we sought to evaluate the factors associated with deaths in the context of severe malnutrition and also the effects of early, i.e., within 3 hours of diagnosing septic shock vs. late blood transfusion. METHODOLOGY: Here, all under-five severely malnourished septic shock children were admitted to ICU during 2013-2017. Children who died constituted cases (n = 54), and the survived (n = 39) represented controls. We excluded children who received the blood transfusion for other causes and who left against medical advice. RESULTS: In both descriptive and multivariate analysis, we found that death was significantly associated with the use of fourth-line antibiotics, corticosteroids, and the addition of vasopressors on top of dopamine (all p < 0.05). However, the decrease of serum calcium level was found significantly associated with death only after adjusting (p < 0.05). Even though the cases more often received early blood transfusion than the controls, the difference was insignificant (p = 0.134). CONCLUSIONS: When a severely malnourished under-five child develops septic shock, requiring vasopressors, fourth-line antibiotic, and corticosteroid, with reduced serum calcium, the probability of death increases significantly. Our findings underscore the gravity of close monitoring at these points and the niches for early interventions.

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial.

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth. Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth. Design, Setting, and Participants: The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat. Interventions: Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea. Main Outcomes and Measures: Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. Results: A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and -0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis. Conclusions and Relevance: The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery diarrhea remains appropriate and should be encouraged. Trial Registration: ClinicalTrials.gov Identifier: NCT03130114.

An Association between Rainy Days with Clinical Dengue Fever in Dhaka, Bangladesh: Findings from a Hospital Based Study.

BACKGROUND: Dengue, a febrile illness, is caused by a Flavivirus transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Climate influences the ecology of the vectors. We aimed to identify the influence of climatic variability on the occurrence of clinical dengue requiring hospitalization in Zone-5, a high incidence area of Dhaka City Corporation (DCC), Bangladesh. METHODS AND FINDINGS: We retrospectively identified clinical dengue cases hospitalized from Zone-5 of DCC between 2005 and 2009. We extracted records of the four major catchment hospitals of the study area. The Bangladesh Meteorological Department (BMD) provided data on temperature, rainfall, and humidity of DCC for the study period. We used autoregressive integrated moving average (ARIMA) models for the number of monthly dengue hospitalizations. We also modeled all the climatic variables using Poisson regression. During our study period, dengue occurred throughout the year in Zone-5 of DCC. The median number of hospitalized dengue cases was 9 per month. Dengue incidence increased sharply from June, and reached its peak in August. One additional rainy day per month increased dengue cases in the succeeding month by 6% (RR = 1.06, 95% CI: 1.04-1.09). CONCLUSIONS: Dengue is transmitted throughout the year in Zone-5 of DCC, with seasonal variation in incidence. The number of rainy days per month is significantly associated with dengue incidence in the subsequent month. Our study suggests the initiation of campaigns in DCC for controlling dengue and other Aedes mosquito borne diseases, including Chikunguniya from the month of May each year. BMD rainfall data may be used to determine campaign timing.

Changing Susceptibility Pattern of Vibrio cholerae O1 Isolates to Commonly Used Antibiotics in the Largest Diarrheal Disease Hospital in Bangladesh during 2000-2018.

The efficacy of commonly used antibiotics for treating severe cholera has been compromised over time because of the reduced antibiotic susceptibility. This study aimed to describe the rate of detection of Vibrio cholerae O1 from fecal samples and antimicrobial susceptibility profiles of V. cholerae O1 serotypes to commonly used antibiotics. During January 2000-December 2018, V. cholerae O1 was detected in fecal samples of 7,472 patients. Vibrio cholerae O1 Inaba serotype was predominant, ranging from 60% to 86% during the period 2000-2006 except for 2003 and 2005 when the Ogawa serotype was predominant. Later on, the Ogawa serotype became predominant from 2007 to 2015, fluctuating between 52% and 100%. However, in 2016 and 2017, isolation rates declined to 2% and 1%, respectively, but surged again to 75% in 2018. Nearly 100% of V. cholerae O1 strains were sensitive to tetracycline during 2000-2004. Thereafter, a declining trend of sensitivity was observed to be continued and dropped down to < 6% during 2012-2017 and again increased to 76% in 2018. Susceptibility to azithromycin and ciprofloxacin was nearly 100%, and susceptibility to cotrimoxazole and furazolidone was 01% throughout the study period. We also found the emergence of resistance to erythromycin in 2005 and sensitivity to cotrimoxazole in 2018. Thus, the rapid decline of the sensitivity of V. cholerae O1 to tetracycline and a reversed peak after 6 years need continued monitoring and reporting.

Comparative Performance of Modified Kenneth Jones Criteria Scoring, World Health Organization Criteria, and Antibodies in Lymphocyte Supernatant for Diagnosing Tuberculosis in Severely Malnourished Children Presenting With Pneumonia.

Background: The diagnosis of childhood tuberculosis (TB) can be difficult in severely malnourished children. This is mainly due to the fact of our perceived notion that clinical signs of TB are often subtle in severely malnourished children and we may rely on laboratory investigation for the diagnosis. However, comparative data on the performance of clinical and laboratory diagnostics of TB in such population are also very limited. Objectives: To compare the performance of composite clinical criteria and a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children with pneumonia. Methods: Severely malnourished children under five with radiological pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh were enrolled consecutively following informed consent. We collected venous blood for ALS, gastric lavage fluid and induced sputum for microscopy, mycobacterial culture, and real-time PCR by Xpert MTB/RIF. We compared the sensitivity, specificity, positive, and negative predictive values, and accuracy of modified Kenneth Jones criteria (MKJC) score, World Health Organization (WHO) criteria, and ALS in diagnosing TB in severely malnourished children with pneumonia for "Confirmed TB" and "All TB" ("Confirmed TB" plus "Probable TB") vs. "Not TB." Results: Compared to culture confirmed TB, the sensitivity, and specificity (95% CI) for MKJC were 60 (27-86) and 84 (79-87)% and for WHO criteria were 40 (14-73) and 84 (80-87)%, respectively. Compared to culture and/or Xpert MTB/RIF positive TB, the sensitivity and specificity (95% CI) for the criteria were 37 (20-58) and 84 (79-87)%; and 22 (9-43) and 83 (79-87)%, respectively. For both these comparisons, the sensitivity and specificity of ALS were 50 (14-86) and 60 (53-67)%, respectively. Conclusion: Our data suggest that WHO criteria and MKJC scoring mainly based on clinical criteria are more useful than ALS in diagnosing TB in young severely malnourished children with pneumonia. The results underscore the importance of using clinical criteria for the diagnosis of TB in severely malnourished children that may help to minimize the chance of over treatment with anti-TB in such population, especially in resource limited TB endemic settings.

Case-Fatality Ratio of Blood Culture-Confirmed Typhoid Fever in Dhaka, Bangladesh.

With impending rollout of new conjugate typhoid vaccines, better estimates of typhoid case-fatality ratio are needed for countries to set priorities for public health programs. We enrolled 1425 patients of all ages with blood culture-confirmed Salmonella Typhi from laboratory networks serving inpatients and outpatients in Dhaka, Bangladesh. Participants were asked about symptoms and complications including death experienced over a median 3-month period following blood culture diagnosis. Four fatal cases were identified (case-fatality ratio of 0.3% [95% confidence interval, .05%-.55%]). Applying this case-fatality ratio to global typhoid burden estimates would reduce deaths by 70%.

Evaluation of a Smartphone Decision-Support Tool for Diarrheal Disease Management in a Resource-Limited Setting.

The emergence of mobile technology offers new opportunities to improve clinical guideline adherence in resource-limited settings. We conducted a clinical pilot study in rural Bangladesh to evaluate the impact of a smartphone adaptation of the World Health Organization (WHO) diarrheal disease management guidelines, including a modality for age-based weight estimation. Software development was guided by end-user input and evaluated in a resource-limited district and sub-district hospital during the fall 2015 cholera season; both hospitals lacked scales which necessitated weight estimation. The study consisted of a 6 week pre-intervention and 6 week intervention period with a 10-day post-discharge follow-up. Standard of care was maintained throughout the study with the exception that admitting clinicians used the tool during the intervention. Inclusion criteria were patients two months of age and older with uncomplicated diarrheal disease. The primary outcome was adherence to guidelines for prescriptions of intravenous (IV) fluids, antibiotics and zinc. A total of 841 patients were enrolled (325 pre-intervention; 516 intervention). During the intervention, the proportion of prescriptions for IV fluids decreased at the district and sub-district hospitals (both p < 0.001) with risk ratios (RRs) of 0.5 and 0.2, respectively. However, when IV fluids were prescribed, the volume better adhered to recommendations. The proportion of prescriptions for the recommended antibiotic azithromycin increased (p < 0.001 district; p = 0.035 sub-district) with RRs of 6.9 (district) and 1.6 (sub-district) while prescriptions for other antibiotics decreased; zinc adherence increased. Limitations included an absence of a concurrent control group and no independent dehydration assessment during the pre-intervention. Despite limitations, opportunities were identified to improve clinical care, including better assessment, weight estimation, and fluid/ antibiotic selection. These findings demonstrate that a smartphone-based tool can improve guideline adherence. This study should serve as a catalyst for a randomized controlled trial to expand on the findings and address limitations.

Medically unexplained illness and the diagnosis of hysterical conversion reaction (HCR) in women's medicine wards of Bangladeshi hospitals: a record review and qualitative study.

BACKGROUND: Frequent reporting of cases of hysterical conversion reaction (HCR) among hospitalized female medical patients in Bangladesh's public hospital system led us to explore the prevalence of "HCR" diagnoses within hospitals and the manner in which physicians identify, manage, and perceive patients whom they diagnose with HCR. METHODS: We reviewed admission records from women's general medicine wards in two public hospitals to determine how often and at what point during hospitalization patients received diagnoses of HCR. We also interviewed 13 physicians about their practices and perceptions related to HCR. RESULTS: Of 2520 women admitted to the selected wards in 2008, 6% received diagnoses of HCR. HCR patients had wide-ranging symptoms including respiratory distress, headaches, chest pain, convulsions, and abdominal complaints. Most doctors diagnosed HCR in patients who had any medically-unexplained physical symptom. According to physician reports, women admitted to medical wards for HCR received brief diagnostic evaluations and initial treatment with short-acting tranquilizers or placebo agents. Some were referred to outpatient psychiatric treatment. Physicians reported that repeated admissions for HCR were common. Physicians noted various social factors associated with HCR, and they described failures of the current system to meet psychosocial needs of HCR patients. CONCLUSIONS: In these hospital settings, physicians assign HCR diagnoses frequently and based on vague criteria. We recommend providing education to increase general physicians' awareness, skill, and comfort level when encountering somatization and other common psychiatric issues. Given limited diagnostic capacity for all patients, we raise concern that when HCR is used as a "wastebasket" diagnosis for unexplained symptoms, patients with treatable medical conditions may go unrecognized. We also advocate introducing non-physician hospital personnel to address psychosocial needs of HCR patients, assist with triage in a system where both medical inpatient beds and psychiatric services are scarce commodities, and help ensure appropriate follow up.

Fatal outbreak from consuming Xanthium strumarium seedlings during time of food scarcity in northeastern Bangladesh.

BACKGROUND: An outbreak characterized by vomiting and rapid progression to unconsciousness and death was reported in Sylhet Distrct in northeastern Bangladesh following destructive monsoon floods in November 2007. METHODS AND FINDINGS: We identified cases presenting to local hospitals and described their clinical signs and symptoms. We interviewed patients and their families to collect illness histories and generate hypotheses about exposures associated with disease. An epidemiological study was conducted in two outbreak villages to investigate risk factors for developing illness. 76 patients were identified from 9 villages; 25% (19/76) died. Common presenting symptoms included vomiting, elevated liver enzymes, and altered mental status. In-depth interviews with 33 cases revealed that 31 (94%) had consumed ghagra shak, an uncultivated plant, in the hours before illness onset. Ghagra shak was consumed as a main meal by villagers due to inaccessibility of other foods following destructive monsoon flooding and rises in global food prices. Persons who ate this plant were 34.2 times more likely (95% CI 10.2 to 115.8, p-value<0.000) than others to develop vomiting and unconsciousness during the outbreak in our multivariate model. Ghagra shak is the local name for Xanthium strumarium, or common cocklebur. CONCLUSIONS: The consumption of Xanthium strumarium seedlings in large quantities, due to inaccessibility of other foods, caused this outbreak. The toxic chemical in the plant, carboxyatratyloside, has been previously described and eating X. strumarium seeds and seedlings has been associated with fatalities in humans and livestock. Unless people are able to meet their nutritional requirements with safe foods, they will continue to be at risk for poor health outcomes beyond undernutrition.

Increasing incidence of post-kala-azar dermal leishmaniasis in a population-based study in Bangladesh.

Post-kala-azar dermal leishmaniasis (PKDL) occurs after kala-azar treatment and acts as a durable infection reservoir. On the basis of active case finding among 22,699 respondents, 813 (3.6%) had had kala-azar since 2002, of whom 79 (9.7%) developed PKDL. Eight additional patients with PKDL had no history of kala-azar. Annual kala-azar incidence peaked at 85 cases per 10,000 person-years in 2004 and fell to 46 cases per 10,000 person-years in 2007, but PKDL incidence rose from 1 case per 10,000 person-years in 2002-2004 to 21 cases per 10,000 person-years in 2007. The rising PKDL incidence threatens the regional visceral leishmaniasis elimination initiative and underscores the urgent need for more effective PKDL diagnosis and treatment.